Ulcerative Colitis: Griffiths A

Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. · Royal Free Hampstead NHS Trust, Centre for Paediatric Gastroenterology, Hampstead, London, UK. · Inflamm Bowel Dis. · Pubmed #18266237 links to  free full text

Abstract: Around 1 in 4 patients with inflammatory bowel disease (IBD) present in childhood, the majority around the time of their pubertal growth spurt. This presents challenges over and above those of managing IBD in adults as this period is a time of dramatic psychological and physical transition for a child. Growth and nutrition are key priorities in the management of adolescents and young adults with IBD. Growth failure in IBD is characterized by delayed skeletal maturation and a delayed onset of puberty, and is best described in terms of height-for-age standard deviation score (Z score) or by variations in growth velocity over a period of 3-4 months. Growth failure is common at presentation in Crohn's disease (CD), but less common in ulcerative colitis (UC). The etiology of growth failure is multifactorial. Principal determinants, however, include the inflammatory process per se, with proinflammatory cytokines (e.g., IL-1beta, IL-6) being directly implicated. Furthermore, poor nutrition and the consequences of prolonged corticosteroid use also contribute to the significant reduction in final adult height of almost 1 in 5 children. Initially a prompt, where possible steroid-free, induction of remission is indicated. The ideal is then to sustain a relapse-free remission until growth is complete, which is often not until early adulthood. These goals can often be achieved with a combination of exclusive enteral nutrition (EEN) and early use of immunosuppressants. The advent of potent and efficacious biological agents considerably improves the range of growth-sparing interventions available to children around puberty, although well-timed surgery remains another highly effective means of achieving remission and significant catch-up growth. We carried out a systematic review of publications to identify the best available evidence for managing growth failure in children with IBD. Despite the paucity of high-quality publications, sufficient data were available in the literature to allow practical, evidence-based where possible, management guidelines to be formulated. Although there is clear evidence that exclusive enteral nutrition achieves mucosal healing, its effect on growth has only been assessed at 6 months. In contrast to corticosteroids, EEN has no negative effect on growth. Corticosteroids remain the key therapy responsible for medication-induced growth impairment, although the use of budesonide in selected patients may minimize the steroid effect on dividing growth plates. Immunosuppressants have become a mainstay of treatment in children with IBD, and are being used earlier in the disease course than ever before. However, there are currently no long-term data reporting better growth outcome if these agents are introduced very soon after diagnosis. In comparison, recent data from a large prospective trial of infliximab in children with moderate to severe CD suggested significant catch-up growth during the first year of regular infusions. The only other intervention that has documented clear catch-up growth has been surgical resection. Resection of localized CD, in otherwise treatment-resistant children, early in the disease process achieves clear catch-up growth within the next 6 months. There are no data available that growth hormone improves final adult height in children with CD. In conjunction with expert endocrinological support, pubertal delay, more common in boys, may be treated with parenteral testosterone if causing significant psychological problems. The optimal management of children and adolescents requires a multidisciplinary approach frequently available within the pediatric healthcare setting. Dedicated dietetic support, along with nurse-specialist, child psychologist, and with closely linked medical and surgical care will likely achieve the best possible start for children facing a lifetime of chronic gut disease.

Kugathasan S, Nebel J, Skelton JA, Markowitz J, Keljo D, Rosh J, LeLeiko N, Mack D, Griffiths A, Bousvaros A, Evans J, Mezoff A, Moyer S, Oliva-Hemker M, Otley A, Pfefferkorn M, Crandall W, Wyllie R, Hyams J, Anonymous00137, Anonymous00138. · Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · J Pediatr. · Pubmed #17961699 No free full text.

Abstract: OBJECTIVE: To conduct a systematic review of children with newly diagnosed inflammatory bowel disease (IBD) from 2 prospective inception cohorts to examine body mass index (BMI) status at presentation. STUDY DESIGN: Clinical, demographic, and BMI data were obtained from 783 patients with newly diagnosed IBD. National Health and Nutrition Examination Survey data for 2748 healthy children were used as a control. RESULTS: Most children with Crohn's disease and ulcerative colitis had a BMI in the normative range (5%-84%). Low BMI (<5%) was seen in 22% to 24% of children with Crohn's disease and 7% to 9% of children with ulcerative colitis. Ten percent of children with Crohn's disease and 20% to 30% of children with ulcerative colitis had a BMI at diagnosis consistent with overweight or risk for overweight. CONCLUSION: Children with IBD are affected by current population trends toward overweight. A significant subgroup of children with newly diagnosed IBD has a BMI categorized as overweight or at risk for overweight. Clinicians should be aware of possible IBD diagnosis in the presence increased BMI.

Mack DR, Langton C, Markowitz J, LeLeiko N, Griffiths A, Bousvaros A, Evans J, Kugathasan S, Otley A, Pfefferkorn M, Rosh J, Mezoff A, Moyer S, Oliva-Hemker M, Rothbaum R, Wyllie R, delRosario JF, Keljo D, Lerer T, Hyams J, Anonymous00371. · Department of Pediatrics, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Ontario, Canada K1H 8L1. · Pediatrics. · Pubmed #17545378 links to  free full text

Abstract: OBJECTIVE: The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease. METHODS: Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospectively in 18 US/Canadian centers. Laboratory values investigated included hemoglobin level, platelet count, albumin level, and erythrocyte sedimentation rate. Disease severity was categorized by physician global assessment. RESULTS: A total of 526 children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with ulcerative colitis) were studied. All 4 values were normal for 21% of patients with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only 3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe ulcerative colitis had normal results for all 4 tests. The erythrocyte sedimentation rate was least likely to be normal; overall, 26% of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate, including 18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet counts for 50%, and albumin levels for 60%. There was no clear association between Crohn disease location and either severity or number of normal laboratory values. In contrast, there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests. CONCLUSION: The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease.

Dassopoulos T, Nguyen GC, Bitton A, Bromfield GP, Schumm LP, Wu Y, Elkadri A, Regueiro M, Siemanowski B, Torres EA, Gregory FJ, Kane SV, Harrell LE, Franchimont D, Achkar JP, Griffiths A, Brant SR, Rioux JD, Taylor KD, Duerr RH, Silverberg MS, Cho JH, Steinhart AH. · Johns Hopkins University Meyerhoff Inflammatory Bowel Disease Center, Baltimore MD, USA. · Inflamm Bowel Dis. · Pubmed #17427244 links to  free full text

Abstract: BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. · Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian, Mezzanine Level, C-Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA. · Science. · Pubmed #17068223 links to  free full text

Abstract: The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.

Hyams J, Markowitz J, Lerer T, Griffiths A, Mack D, Bousvaros A, Otley A, Evans J, Pfefferkorn M, Rosh J, Rothbaum R, Kugathasan S, Mezoff A, Wyllie R, Tolia V, delRosario JF, Moyer MS, Oliva-Hemker M, Leleiko N, Anonymous00069. · Connecticut Children's Medical Center, Hartford, Connecticut, USA. · Clin Gastroenterol Hepatol. · Pubmed #16820327 No free full text.

Abstract: BACKGROUND & AIMS: The aim of this study was to determine the clinical outcome after corticosteroid therapy in children who are newly diagnosed with ulcerative colitis (UC). METHODS: Data were gathered prospectively from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry database between January 2002 and March 2005. All children who were newly diagnosed with inflammatory bowel disease younger than the age of 16 years were managed according to the dictates of their respective physicians. Demographic, clinical, and laboratory data were collected at diagnosis, at 30 days, and then quarterly. Patients were classified as corticosteroid responsive, corticosteroid dependent, or refractory, and outcomes were determined at 3 months and at 1 year. RESULTS: Ninety-seven patients had a diagnosis of UC and a minimum of 1 year of follow-up evaluation; 77 (79%) received corticosteroids (62 within 30 days of diagnosis [early] and 15 between 31 days and 6 months [late]). At diagnosis, 81% of corticosteroid-treated patients (age, 11.3 +/- 3.5 y) had moderate/severe disease, and 81% had pancolitis. For those treated early with corticosteroids, disease activity at 3 months was inactive in 60%, mild in 27%, and moderate/severe in 11%. At 1 year, 31 of 62 (50%) of the early corticosteroid-treated patients were considered corticosteroid responsive and 28 (45%) were corticosteroid dependent. A total of 4 patients receiving corticosteroids (5%) required colectomy in the first year. Immunomodulators were used in 61% of all corticosteroid-treated patients. CONCLUSIONS: Although short-term clinical response to corticosteroids in children with newly diagnosed UC is excellent, even with the common use of immunomodulators corticosteroid dependence is seen in 45% of patients.